It has long been recognized that the fluorescent and phosphorescent properties of certain materials vary in accordance with properties of the surroundings. For example, certain luminescent materials are subject to "quenching" or extinction of their luminescent response by oxygen. Various instruments have been proposed to exploit such phenomena in chemical and/or physical measuring instruments. For example, U.S. Pat. No. 4,810,655 discloses an instrument for determining oxygen concentration by applying excitation light to a fluorescent material and observing the time dependence of fluorescence decay. As the oxygen concentration in the environment surrounding the luminescent material changes, the pattern of fluorescent decay with time also changes. The '655 instrument employs a "light pipe" for transmitting the requisite excitation light to the luminescent material and for transmitting the light back to a sensor. European Patent Application 0,283,289 monitors the intensity of long lived phosphorescent emissions from a phosphorescent material bonded to an end of an optical fiber. The optical fiber is small enough that it can be inserted through a small tube, such as an intravenous catheter or the like, so that the phosphorescent material lies within a blood vessel and acts as an in vivo PO.sub.2 sensor. Other fiber optic based PO.sub.2 sensors are disclosed in U.S. Pat. No. 4,476,870 and European Patent Application 0,252,578. U.S. Pat. No. 4,576,173 discloses an instrument for monitoring relatively long-lived "singlet oxygen emission" or phosphorescence exhibited by certain bodily tissues such as tumors when those tissues are treated with photosensitizing chemicals and exposed to incident light. This instrument employs a chopped or pulsatile incident light. In order to segregate the relatively long-lived "singlet oxygen emissions" or phosphorescence from the relatively short lived fluorescence of the sensitizing chemicals, the instrument employs a quadrature detection system. A signal in phase with the chopped excitation light is segregated from the quadrature component 90 degrees out of phase with the chopped excitation light signal. The quadrature signal, out of phase with the chopping signal, consists essentially of the desired long-lived "singlet oxygen emission" signal. Although the reference mentions "frequency domain signal processing", the signal processing involved is nothing more than isolation of the quadrature signal from the in phase signal. The amplitude of the isolated quadrature signal is monitored to monitor the desired "singlet oxygen emission" intensity.
Although these and other fiber optic based luminescence probes and instruments have been proposed for monitoring chemical and/or physical conditions within the bodies of living subjects, the instruments available heretofore have suffered from certain significant drawbacks. For ease of insertion into the body, a fiber optic probe should be less than about 450 micrometers in diameter. It is especially important to keep the diameter of each fiber optic probe to a minimum when a plurality of fiber optic probes are to be passed into the body through a single opening, as through a lumen of a single intravascular catheter or hypodermic needle. The amount of luminescent material which can be accommodated in a probe of such small diameter is limited. Moreover, the total energy which can be applied to the luminescent material by excitation light transmitted along the fiber optic is directly proportional to the cross-sectional area of the fiber optic. Thus, only limited light energy can be applied to excite the luminescent material in a fiber optic probe. All of these factors tend to limit the amplitude of the response light emitted by the luminescent material and transmitted back along the fiber to the proximal end. Even highly sensitive photodetectors will provide only a weak signal. Further, the signal is susceptible to interference from many sources, including changes in optical and/or electronic components with time. The weak response signal from the actual luminescent material at the probe may be effectively hidden by the background noise. Stated another way, such instruments have had poor signal to noise ratios. This problem has been particularly severe in the case of instruments arranged to monitor the decay rate of relatively short-lived luminescent phenomena such as fluorescence or rapidly-decaying phosphorescence.
Thus, prior to the present invention, there have been significant, unmet needs for still further improvement in luminescence based biomedical monitoring apparatus and methods.